A small population of vasculitogenic T cells expands and has skewed T cell receptor usage after culture with syngeneic smooth muscle cells

Autor: Matyas Sandor, Dana C. Baiu, Zsuzsa Fabry, Michael N. Hart, Brad J Swanson
Rok vydání: 2003
Předmět:
Zdroj: Journal of Autoimmunity. 20:125-133
ISSN: 0896-8411
DOI: 10.1016/s0896-8411(02)00113-0
Popis: Adoptive transfer of lymphocytes co-cultured with syngeneic smooth muscle (SM) cells to healthy recipient mice results in vasculitic lesions predominantly in post-capillary venules. The present study focuses on the mechanisms by which the disease-inducing CD4(+) T cells are generated in co-culture of lymphocytes with SM cells. Microvascular SM cells provide survival signals to both CD4(+) and CD8(+) naïve syngeneic T cells and can activate only a limited range of CD4(+) T lymphocytes in culture. Additionally, approximately 0.4% of the original CD4(+) T cells divide at least twice in co-culture with SM cells. Survival of CD4(+) T cells in co-culture is dependent on a TCR mediated process, since transgenic CD4 (+)cells with a unique specificity for a non-murine peptide do not survive in culture with SM. Analysis of TCR Vbeta shows no superantigen activation of T cells following co-culture with SM cells. Spectratype analysis of TCR Vbeta Jbeta segment usage reveals a skewage in the TCR repertoire of T cells co-cultured with SM, and also of T cells from vasculitic lung. These results are consistent with a specific immune response of pathogenic T cells against one or more activating antigenic determinants of the microvascular SM cells, in contrast to non-specific cytokine activation.
Databáze: OpenAIRE